Evidence has accumulated in animal systems that aflatoxin B1 or a transformed intermediate is O-demethylated and/or hydroxylated. Presumably these reactions result from enzymatic activity of the liver endoplasmic reticulum, specifically the mixed-function-oxidase complex (MFO). Although the relationship of aflatoxin metabolism to other metabolites and environmental toxicants is not well defined, there is the suggestion that particular types of materials, including food additives as well as certain dietary regimens, potentiate the effects of fungal toxins. In the present study, metabolic transformations of aflatoxin (e.g., B1) will be investigated in reference to the enzymology of the MFO system, and to the chemical identification of metabolites produced in vitro by endoplasmic reticulum of human liver samples obtained at biopsy. The effects of substances known to increase or decrease carcinogenic response to aflatoxin in animals will be evaluated for their ability to influence the metabolic transformation of more potent toxins to less potent forms in human liver (in vitro). Animal models will be employed to produce sufficient quantities of metabolites (identical to those produced by human liver in vitro) for toxicity evaluation and for subcellular purification of MFO components essential to aflatoxin metabolism. The study deals with a critical aspect of carcinogen metabolism.